Time-Of-Flight Instrument with Variable Ionization Sources: We identified two very critical problems in the mass spectrometry facility of the Department of Chemistry at the University of Pennsylvania: (1) A lacking capability to routinely measure high-resolution data for a broad range of compounds and (2) a lacking capability to routinely analyze larger synthetic molecules and biomolecules. The requested Time-Of-Flight (TOF) instrument from Agilent will completely solve these critical problems. The proposed instrument consists of a TOF mass analyzer and multiple atmospheric pressure ionization sources. The TOF analyzer is designed to simultaneously provide excellent mass accuracy (< 3 ppm), high mass resolution (> 13,000), large dynamic range (3.5 decades), and fast spectral acquisition rates (20-40 spectra/sec) for the mass/charge (m/z) range of 50-12,000. The multiple atmospheric pressure ionization sources include electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and matrix- assisted laser desorption/ionization (MALDI). The instrument was selected because it uniquely combines (1) the ability to determine accurate masses over a large m/z range, (2) the capability to analyze a very broad range of compound classes due to interchangeable ionization sources, and (3) because the design of the instrument and the software allow the measurement of samples in a routine walk-up fashion. These three properties make this instrument ideal for the multi-user environment in the Chemistry Department at the University of Pennsylvania. The proposed instrument will meet all the critical and currently unfulfilled needs of 12 NIH-supported researchers (major user group) concerned with the design, synthesis, and evaluation of synthetic and natural molecules such as small molecules, small and natural products, unnatural oligomers, natural and modified peptides, peptidomimetics, natural and artificial oligonucleotides, and small proteins. It is estimated that over five years, the instrument would impact significantly the research programs of around 20 NIH-funded investigators in the Chemistry Department at the University of Pennsylvania. [unreadable] [unreadable] [unreadable]